Work

Spermidine Attenuates Sepsis-associated Acute Lung Injury by Targeting Macrophage Apoptosis via PI3K/Akt Signaling Axis

Year: 2026

Type: article

Abstract: Background Sepsis-associated acute lung injury (SALI) is characterized by an uncontrolled inflammatory response and cell apoptosis, with macrophage apoptosis playing a key role in alveolar barrier disruption. Spermidine (SP), as a natural polyamine, has shown potential in anti-aging and immune regulation, but its intervention effect and mechanism on macrophage apoptosis in SALI are not yet clear. Purpose This study aimed to investigate the interventional effect of SP on macrophage apoptosis in SALI and to elucidate its potential molecular mechanism. Materials and Methods A mouse SALI model was constructed by cecal ligation, and the intervention was performed by intraperitoneal administration of SP. Observe the phenotype of lung injury in SALI mice and the release of pro-inflammatory cytokines. Mechanistically, network pharmacology analysis was used to determine the potential mechanism of SP treatment for SALI and conduct experimental validation. Results The results showed that SP treatment significantly reduced the wet-to-dry ratio of lung tissue and the amount of protein exudation in bronchoalveolar lavage fluid, inhibiting the release of pro-inflammatory factors interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and alleviating alveolar structural damage. Mechanistically, we employed network pharmacology analysis to indicate that the key mechanism of SP’s therapeutic effect on SALI lies in its anti-apoptotic properties. Immunoblot analysis further showed that SP treatment reduced the expression of pro-apoptotic proteins cleaved-caspase 9/3, and Bax in lung tissue, while upregulating the anti-apoptotic protein Bcl-2. Conclusion This study elucidates for the first time the mechanism by which SP alleviates SALI by targeting the macrophage apoptosis pathway, providing experimental evidence for the development of lung protection strategies based on immune metabolism regulation.

Source: Pharmacognosy Magazine

DOI: 10.1177/09731296261417098

Authors: Pengcheng Shen, Ying Lan, Zhe Bai

Institution: Chengdu University

Language: English

Topic: Sepsis Diagnosis and Treatment

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $1,600